Ask about this productRelated genes to: MSH2 antibody
- Gene:
- MSH2 NIH gene
- Name:
- mutS homolog 2
- Previous symbol:
- COCA1
- Synonyms:
- HNPCC, HNPCC1
- Chromosome:
- 2p21-p16.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-07-28
- Date modifiied:
- 2019-04-23
Related products to: MSH2 antibody
Related articles to: MSH2 antibody
- The aim of this study is to assess the mismatch repair (MMR) status and immunohistochemical changes in cases of recurrent endometrial cancer following primary surgery and to evaluate the impact of these changes on prognosis. Thirty-one patients diagnosed with endometrial cancer who underwent surgery and had pathologically confirmed recurrences were evaluated. Changes in MMR protein expression, estrogen receptor (ER)/progesterone receptor (PR), and p53 expression in primary surgery and recurrent tumor tissues were assessed using immunohistochemical methods. Prognostic factors influencing these parameters and survival data were investigated. : In the assessment of recurrent materials, there were four cases where the MLH-1&PMS-2 staining status changed from intact to loss and four cases that changed from loss to intact. No changes were observed in regard to MSH-2 &MSH-6 staining. The ratios of pMMR and dMMR following the primary surgery were 55% (n = 17) and 45% (n = 14), respectively. Four cases transitioned from pMMR to dMMR, and four cases transitioned from dMMR to pMMR. After recurrence, changes in the ER, PR, and P53 status were observed in seven, three, and three patients, respectively. : Changes in the MMR status, receptors, and P53 were observed. It is necessary to re-evaluate prognostic parameters via biopsies in recurring cases and to adjust rescue treatments accordingly. - Source: PubMed
Publication date: 2026/04/27
Guzeloz ZelihaKutlu OzceErdogan OzgurDemir GonulGulle Bugra TaygunSancı MuzafferErdogan MihribanTalu Canan Kelten - Endometrial carcinoma (EC) is now classified primarily by molecular subtype--ultramutated, mismatch repair-deficient (dMMR), -mutant/copy-number-high (CNH), and "no specific molecular profile" (NSMP)-a framework that has reshaped prognostic counseling and adjuvant therapy decisions. Yet several practically important questions remain insufficiently addressed in real-world cohorts: whether all four mismatch repair genes confer an equivalent favorable prognosis, whether all alterations carry the same survival benefit or only specific pathogenic variants, and whether molecular subtypes retain prognostic value after adjustment for histology and tumor burden. We addressed these questions in 2901 patients pooled from the MSK-IMPACT 50K Clinical Sequencing Cohort ( = 2372; discovery) and the TCGA UCEC PanCancer Atlas ( = 529; validation)-the largest dual-cohort genomic analysis of EC reported to date. We performed individual MMR gene and combined dMMR survival stratification, multivariable Cox regression adjusted for age, histology, and sample type, and a pathogenicity-aware sensitivity analysis for POLE variants, with tumor mutational burden (TMB) compared across subgroups. Across both cohorts, all four MMR gene-mutant subgroups (, , , ) conferred equivalently favorable overall survival (OS) (six-group log-rank = 7.66 × 10 in discovery; = 6.78 × 10 in validation), confirming dMMR as a class-level prognostic designation independent of which MMR gene is altered. Multivariable Cox regression demonstrated that -ultramutated status retained an independent favorable effect (HR = 0.62, = 0.038 in MSK; HR = 0.35, = 0.028 in TCGA) after adjustment for age, histology, and sample type, while the favorable dMMR effect was largely accounted for by histologic context. Critically, a pathogenicity-aware sensitivity analysis revealed that the exceptional survival of the subgroup is confined to canonical exonuclease-domain hotspot mutations (event rate 0.9% in MSK), whereas variants of uncertain significance behave indistinguishably from NSMP-like tumors. Consistent with this finding, TMB was markedly elevated in canonical pathogenic cases (median 138.7 mut/Mb in MSK; 247.4 in TCGA) but not in -VUS-only cases (median 29.0 and 15.0, respectively; < 0.001 between groups in both cohorts), confirming that the ultramutator phenotype is confined to canonical pathogenic variants. We additionally characterize Uterine Clear Cell Carcinoma as a distinct histologic entity ( = 73; 3.0%) and report the + co-mutant group ( = 90; 3.8%). These findings refine the molecular classification of EC in clinically meaningful ways: they support class-level immunotherapy eligibility based on dMMR status regardless of the specific MMR gene altered, demonstrate that -ultramutated classification requires variant-level pathogenicity assessment, and identify -mutant/CNH patients as the population with the most urgent unmet therapeutic need. - Source: PubMed
Publication date: 2026/05/21
Sertesen Çamöz ElifKarabuğa BerkanKaraçin CengizTerzi Yunus KasımYılmaz Çelik Zerrin - Cancer frequently clusters in families due to shared environment and genetics. However, many familial cancer cases lack a clinically recognized pathogenic germline variant (PGV). We analyzed germline genomes and family history from 2,726 individuals without a PGV in the All of Us Research Program, including 1,496 cases across 18 cancer types with extensive family history and 1,230 family history-negative, cancer-free controls. We identified allelic series of rare structural variants inactivating in individuals with phenotypes consistent with Lynch syndrome and in breast cancer. Cancer polygenic risk scores were enriched in cases and correlated with patterns of cancer diagnoses within families. Exome-wide rare variant analyses nominated six candidate predisposition genes, including and in thyroid and breast cancer, respectively. Overall, polygenic risk and rare variants impacting known genes explained a median of 5% of unexplained familial cancers, increasing to 11% when including newly nominated risk factors. - Source: PubMed
Publication date: 2026/05/13
Fields NoahHan SeunghunMei WenbinShannon ErinBuehler RyanNeklason DeborahPimenta EricaKamihara JunneGarber JudyGillani RiazAlDubayan SaudPark JihyeCollins Ryan LVan Allen Eliezer M - To characterize tumor-site distribution, age at diagnosis, sex distribution, and tumor multiplicity in a Brazilian institutional Lynch syndrome (LS) cohort stratified by mismatch repair (MMR) gene and genetic testing status, and to assess the impact of including nontested (NT) relatives. - Source: PubMed
Publication date: 2026/05/20
Bassaneze ThiagoOliveira Ferreira FábioSandoval Renata LazariPisani Janina PontesVanessa Quirino CarlaRodrigues de Nicola Pablo DomingosAchatz Maria IsabelDominguez-Valentin MevRossi Benedito Mauro - Comparison of immunohistochemical detection of mismatch repair (MMR) proteins within tumours, as deficient MMR is important for (1) the detection of Lynch Syndrome, caused by inherited variants affecting the DNA MMR genes and , (2) aiding MMR gene variant interpretation and (3) deciding on use of immune checkpoint blockade therapy. - Source: PubMed
Publication date: 2026/05/19
Farmkiss Luke ArDodson AndrewParry SuzanneJames Michelle CharmaineFrayling Ian MArends Mark Johan